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1.
J Antimicrob Chemother ; 75(12): 3485-3490, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32830242

RESUMEN

BACKGROUND: The incidence of antimicrobial-resistant Neisseria gonorrhoeae (GC) is rising in Canada; however, antimicrobial resistance (AMR) surveillance data are unavailable for infections diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs), representing over 80% of diagnoses. We developed a set of 10 improved molecular assays for surveillance of GC-AMR and prediction of susceptibilities in NAAT specimens. METHODS: Multiplex real-time PCR (RT-PCR) assays were developed to detect SNPs associated with cephalosporin (ponA, porB, mtrR -35delA, penA A311V, penA A501, N513Y, G545S), ciprofloxacin (gyrA S91, parC D86/S87/S88) and azithromycin [23S (A2059G, C2611T), mtrR meningitidis-like promoter] resistance. The assays were validated on 127 gonococcal isolates, 51 non-gonococcal isolates and 50 NAATs with matched culture isolates. SNPs determined from the assay were compared with SNPs determined from in silico analysis of WGS data. MICs were determined for culture isolates using the agar dilution method. RESULTS: SNP analysis of the 50 NAAT specimens had 96% agreement with the matched culture RT-PCR analysis. When compared with MICs, presence of penA A311V or penA A501 and two or more other SNPs correlated with decreased susceptibility and presence of three or more other SNPs correlated with intermediate susceptibility to cephalosporins; presence of any associated SNP correlated with ciprofloxacin or azithromycin resistance. NAAT-AMR predictions correlated with matched-culture cephalosporin, ciprofloxacin and azithromycin MICs at 94%, 100% and 98%, respectively. CONCLUSIONS: We expanded molecular tests for N. gonorrhoeae AMR prediction by adding new loci and multiplexing reactions to improve surveillance where culture isolates are unavailable.


Asunto(s)
Gonorrea , Neisseria gonorrhoeae , Antibacterianos/farmacología , Azitromicina/farmacología , Canadá , Cefalosporinas/farmacología , Ciprofloxacina/farmacología , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
2.
Can Commun Dis Rep ; 45(6): 164-169, 2019 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-31285709

RESUMEN

BACKGROUND: Many countries have experienced increases in invasive meningococcal disease (IMD) due to a serogroup W Neisseria meningitidis (MenW) strain of the multilocus sequence type (ST)-11 clonal complex (CC). MenW ST-11 was first reported in Ontario, Canada, in 2014. By 2016, this strain caused IMD in five provinces and was responsible for 18.8% of the IMD cases in Canada. OBJECTIVE: To provide an update on invasive MenW disease in Canada including the strain characteristics, specimen source of isolates, age, sex and geographic distribution of cases. METHODS: N. meningitidis from culture-positive IMD cases are routinely submitted to the National Microbiology Laboratory (NML) for serogroup, serotype, serosubtype and sequence type analysis. The data from January 1, 2016 to December 31, 2018 were analyzed by calculating the proportion of IMD cases caused by MenW compared with other serogroups. In addition, trends based on age, sex and geographic distribution of cases and specimen source of isolates were analyzed based on information on specimen requisition forms. RESULTS: Over the 3-year period, 292 individual IMD case isolates were analyzed. The percentage of IMD case isolates typed as MenW more than doubled from 19% (n=15) to 44% (n=51) in 2018 when MenW became the most common serogroup, exceeded the number of MenB, MenC or MenY. In total, 93 MenW case isolates were identified, 91% (n=85) belonged to the ST-11 CC. The increase in MenW affected all age groups (but was most common in those older than 60) and both sexes, and occurred across the country but most prevalent in western Canada. The most common specimen source was blood. CONCLUSION: In 2018, MenW was the most common serogroup for isolates received by the NML from culture-positive IMD cases in Canada. Over 90% of the MenW serogroup isolates belonged to the ST-11 CC. The quadrivalent ACWY meningococcal conjugate vaccine protects against IMD caused by strains in the A, C, W or Y serogroups and therefore may protect against IMD caused by the new MenW ST-11 strain; however, more research is needed. The emergence of variant strains highlight the importance of strain characterization in IMD surveillance and research.

3.
Vaccine ; 37(31): 4243-4245, 2019 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-31239214

RESUMEN

In the Saguenay-Lac-Saint-Jean region of Quebec, 83% of the population ≤20 years (n ≅ 59,500) was immunized in 2014 with the four-component Serogroup B meningococcal vaccine to control a long-lasting outbreak caused by a virulent ST-269 Serogroup B Neisseria meningitidis clone. Following the campaign, invasive meningococcal B disease (B-IMD) incidence fell sharply in the target population from 11.4/100,000 in 2006-2014 to 0.4/100,000 in 2014-2018 (p < 0.0001). Five B-IMD cases occurred in the region from July 2014 to June 2018, including one vaccinated child, one unvaccinated young adult and 3 unvaccinated elderly adults. Estimate of direct vaccine protection was 79% [95%CI:-231%;99%]. The overall campaign impact in the region taking into account the decrease in B-IMD incidence at provincial level was a 86% [95%CI:-2%;98%] decrease in B-IMD risk. The campaign impact was mostly seen in the target age-group suggesting no herd effect among unvaccinated older adults.


Asunto(s)
Programas de Inmunización , Meningitis Meningocócica/prevención & control , Neisseria meningitidis Serogrupo B/inmunología , Vacunación , Adulto , Anciano , Brotes de Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Quebec/epidemiología , Vacunación/métodos , Adulto Joven
4.
Can Commun Dis Rep ; 45(2-3): 45-53, 2019 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31015818

RESUMEN

BACKGROUND: Neisseria gonorrhoeae have acquired resistance to many antimicrobials, including third generation cephalosporins and azithromycin, which are the current gonococcal combination therapy recommended by the Canadian Guidelines on Sexually Transmitted Infections. OBJECTIVE: To describe antimicrobial susceptibilities for N. gonorrhoeae circulating in Canada between 2012 and 2016. METHODS: Antimicrobial resistance profiles were determined using agar dilution of N. gonorrhoeae isolated in Canada 2012-2016 (n=10,167) following Clinical Laboratory Standards Institute guidelines. Data were analyzed by applying multidrug-resistant gonococci (MDR-GC) and extensively drug-resistant gonococci (XDR-GC) definitions. RESULTS: Between 2012 and 2016, the proportion of MDR-GC increased from 6.2% to 8.9% and a total of 19 cases of XDR-GC were identified in Canada (0.1%, 19/18,768). The proportion of isolates with decreased susceptibility to cephalosporins declined between 2012 and 2016 from 5.9% to 2.0% while azithromycin resistance increased from 0.8% to 7.2% in the same period. CONCLUSION: While XDR-GC are currently rare in Canada, MDR-GC have increased over the last five years. Azithromycin resistance in N. gonorrhoeae is established and spreading in Canada, exceeding the 5% level at which the World Health Organization states an antimicrobial should be reviewed as an appropriate treatment. Continued surveillance of antimicrobial susceptibilities of N. gonorrhoeae is necessary to inform treatment guidelines and mitigate the impact of resistant gonorrhea.

5.
Can J Infect Dis Med Microbiol ; 2017: 4347206, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28246534

RESUMEN

Background. In Canada, the current recommendation is to offer PPV23 to adults ≥ 65 years. PCV13 is now licensed for adults. Methods. Invasive pneumococcal disease (IPD) cases in adults 65-74 years of age in the Quebec notifiable diseases registry were classified into five serotype categories. Poisson regression models were fitted to monthly rates observed in 2000-2014 and predictions were made for 2015-2024, using theoretical assumptions regarding indirect effects of childhood vaccination and serotype replacement. Results. IPD rates caused by PCV7 serotypes decreased markedly since PCV7 introduction for children in December 2004. This trend is also underway for additional PCV13 serotypes except serotype 3. Additional PPV23 serotypes and nonvaccine serotypes have been on rise since 2004 and this is expected to continue. A small decrease in overall IPD incidence in the next decade is predicted. The proportion of PCV13 serotypes represented 33% of IPD cases in 2014 and would be 20% (95% CI: 15% to 28%) in 2024. PPV23 coverage was 53% in 2014 and is expected to be 47% (95% CI: 26% to 85%) in 2024. Conclusion. The potential usefulness of a combined PCV13 + PPV23 program for elderly adults would decrease over time but PCV13 would be the only option to prevent serotype 3 IPD.

7.
J Hosp Infect ; 93(1): 29-34, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26876749

RESUMEN

BACKGROUND: Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) is an increasingly important cause of healthcare-associated infection. Uncertainties remain concerning optimal control measures for healthcare-associated outbreaks. AIM: To describe the epidemiology and control of an XDR-Ab outbreak that involved multiple units of a large hospital from March 2012 to January 2014. METHODS: Case-finding included screening of rectum, groin, throat, nose, wounds, iatrogenic portals of entry, and catheterized sites. Antimicrobial susceptibility was evaluated by disc diffusion and E-test. Resistance genes were detected by polymerase chain reaction. Clonality was assessed by pulsed-field gel electrophoresis. Charts of cases were reviewed to identify risk factors for invasive infection. Control measures included isolation and cohorting of cases, hand hygiene reinforcement, environmental decontamination, and source control with daily baths using wipes pre-impregnated with chlorhexidine gluconate. FINDINGS: A single clonal strain of XDR-Ab colonized or infected 29 patients. Five patients died of XDR-Ab bacteraemia. Transmission occurred primarily on two wards. Colonization was detected at all anatomical screening sites; only 57% (16/28) of cases were rectal carriers. Advanced malignancy was a risk factor for bacteraemia (relative risk: 5.8; 95% confidence interval: 1.2-27.0). Transmission ended following implementation of the multimodal control strategy. No additional nosocomial cases occurred during the following 20 months. CONCLUSION: Our study highlights the need to screen multiple anatomic sites to diagnose carriage and identifies risk factors for XDR-Ab bacteraemia. A multimodal intervention that included daily chlorhexidine baths for cases was rapidly followed by the termination of the outbreak. Hospitals should consider similar interventions when managing future XDR-Ab outbreaks.


Asunto(s)
Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/aislamiento & purificación , Baños/métodos , Clorhexidina/administración & dosificación , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Desinfectantes/administración & dosificación , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/prevención & control , Acinetobacter baumannii/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Pruebas Antimicrobianas de Difusión por Disco , Farmacorresistencia Bacteriana Múltiple , Electroforesis en Gel de Campo Pulsado , Femenino , Genes Bacterianos , Humanos , Control de Infecciones/métodos , Masculino , Persona de Mediana Edad , Tipificación Molecular , Reacción en Cadena de la Polimerasa
8.
PLoS One ; 11(1): e0146539, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26808518

RESUMEN

BACKGROUND: Dengue is a major international public health concern, one of the most important arthropod-borne diseases. More than 3.5 billion people are at risk of dengue infection and there are an estimated 390 million dengue infections annually. This prolific increase has been connected to societal changes such as population growth and increasing urbanization generating intense agglomeration leading to proliferation of synanthropic mosquito species. Quantifying the spatio-temporal epidemiology of dengue in large cities within the context of a Geographic Information System is a first step in the identification of socio-economic risk factors. METHODOLOGY/PRINCIPAL FINDINGS: This Project has been approved by the ethical committee of Institut Pasteur. Data has been anonymized and de-identified prior to geolocalisation and analysis. A GIS was developed for Delhi, enabling typological characterization of the urban environment. Dengue cases identified in the Delhi surveillance system from 2008 to 2010 were collated, localised and embedded within this GIS. The spatio-temporal distribution of dengue cases and extent of clustering were analyzed. Increasing distance from the forest in Delhi reduced the risk of occurrence of a dengue case. Proximity to a hospital did not increase risk of a notified dengue case. Overall, there was high heterogeneity in incidence rate within areas with the same socio-economical profiles and substantial inter-annual variability. Dengue affected the poorest areas with high density of humans, but rich areas were also found to be infected, potentially because of their central location with respect to the daily mobility network of Delhi. Dengue cases were highly clustered in space and there was a strong relationship between the time of introduction of the virus and subsequent cluster size. At a larger scale, earlier introduction predicted the total number of cases. CONCLUSIONS/SIGNIFICANCE: DENV epidemiology within Delhi has a forest fire signature. The stochastic nature of this invasion process likely smothers any detectable socio-economic risk factors. However, the significant finding that the size of the dengue case cluster depends on the timing of its emergence emphasizes the need for early case detection and implementation of effective mosquito control. A better understanding of the role of population mobility in contributing to dengue risk could also help focus control on areas at particular risk of dengue virus importation.


Asunto(s)
Dengue/epidemiología , Brotes de Enfermedades , Virus del Dengue , Humanos , India/epidemiología , Control de Mosquitos , Factores de Riesgo , Factores Socioeconómicos , Urbanización
9.
Emerg Infect Dis ; 22(1): 65-7, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26689114

RESUMEN

Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010-2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Canadá , Humanos , Pruebas de Sensibilidad Microbiana/métodos
11.
J Clin Microbiol ; 53(7): 2042-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25878350

RESUMEN

The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ≥2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results.


Asunto(s)
Antibacterianos/farmacología , Cefalosporinas/farmacología , Farmacorresistencia Bacteriana , Marcadores Genéticos , Técnicas de Genotipaje/métodos , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Canadá , Femenino , Genes Bacterianos , Gonorrea/microbiología , Humanos , Masculino , Técnicas Microbiológicas/métodos , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y Especificidad
12.
Lett Appl Microbiol ; 59(2): 193-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24712310

RESUMEN

UNLABELLED: Haemophilus influenzae serotype a (Hia) has become an important pathogen in the post-H. influenzae serotype b (Hib) vaccine era. Antibiotic resistance in H. influenzae is a global phenomenon, but few studies have looked at antibiotic resistance profiles with regard to serotype. Invasive Hia (n = 157), noninvasive Hia (n = 2) and invasive Hib (n = 42) collected over the last two decades from three Canadian Provinces were examined for resistance to several commonly prescribed antibiotics, and sequence types (STs) were determined by MLST. Only 1·9% of Hia showed antibiotic resistance, while 31% of Hib were resistant to one or more antibiotic. Resistance to ampicillin, sulfamethoxazole-trimethoprim, chloramphenicol and tetracycline was observed, with ß-lactamase-mediated ampicillin resistance being the most common. Nine STs were identified for Hia with 7 STs belonging to the same clonal complex. Ten STs were observed in Hib strains, and all of them belonged to a single clonal complex. A possible correlation between sequence type and ampicillin resistance was observed for Hib, while no correlations were observed for Hia. SIGNIFICANCE AND IMPACT OF THE STUDY: Despite H. influenzae serotype b (Hib) vaccine programs, invasive disease due to Hib still exists in Canada and is either second or third most common behind nontypeable and/or serotype a (Hia). Many previous studies on antibiotic resistance have focussed on respiratory isolates, and few have looked at resistance with regard to serotype. This study analysed antibiotic resistance in invasive Hia and Hib collected over 20 years from three provinces, and results found that significantly more Hib showed resistance compared to Hia. This provides a small snapshot of H. influenzae disease in Canada and highlights the importance to continually monitor antibiotic resistance profiles.


Asunto(s)
Ampicilina/farmacología , Antibacterianos/farmacología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a la Ampicilina , Proteínas Bacterianas/genética , Niño , Preescolar , Pruebas Antimicrobianas de Difusión por Disco , Haemophilus influenzae/clasificación , Haemophilus influenzae/genética , Humanos , Lactante , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Serogrupo , Adulto Joven , beta-Lactamasas/genética
13.
J Antimicrob Chemother ; 69(7): 1825-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24659751

RESUMEN

OBJECTIVES: An increasing prevalence since 2010 of Serratia marcescens harbouring the Ambler class A carbapenemase SME prompted us to further characterize these isolates. METHODS: Isolates harbouring bla(SME) were identified by PCR and sequencing. Phenotypic analysis for carbapenemase activity was carried out by a modified Hodge test and a modified Carba NP test. Antimicrobial susceptibilities were determined by Etest and Vitek 2. Typing was by PFGE of macrorestriction digests. Whole-genome sequencing of three isolates was carried out to characterize the genomic region harbouring the bla(SME)-type genes. RESULTS: All S. marcescens harbouring SME-type enzymes could be detected using a modified Carba NP test. Isolates harbouring bla(SME) were resistant to penicillins and carbapenems, but remained susceptible to third-generation cephalosporins, as well as fluoroquinolones and trimethoprim/sulfamethoxazole. Isolates exhibited diverse genetic backgrounds, though 57% of isolates were found in three clusters. Analysis of whole-genome sequence data from three isolates revealed that the bla(SME) gene occurred in a novel cryptic prophage genomic island, SmarGI1-1. CONCLUSIONS: There has been an increasing occurrence of S. marcescens harbouring bla(SME) in Canada since 2010. The bla(SME) gene was found on a genomic island, SmarGI1-1, that can be excised and circularized, which probably contributes to its dissemination amongst S. marcescens.


Asunto(s)
Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Islas Genómicas , Infecciones por Serratia/microbiología , Serratia marcescens/enzimología , Serratia marcescens/genética , beta-Lactamasas/análisis , beta-Lactamasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Canadá , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Femenino , Transferencia de Gen Horizontal , Variación Genética , Humanos , Secuencias Repetitivas Esparcidas , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Datos de Secuencia Molecular , Tipificación Molecular , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Serratia marcescens/aislamiento & purificación
14.
J Antimicrob Chemother ; 69(3): 637-42, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24275114

RESUMEN

OBJECTIVES: Emergence of plasmids harbouring bla(NDM-1) is a major public health concern due to their association with multidrug resistance and their potential mobility. METHODS: PCR was used to detect bla(NDM-1) from clinical isolates of Providencia rettgeri (PR) and Klebsiella pneumoniae (KP). Antimicrobial susceptibilities were determined using Vitek 2. The complete DNA sequence of two bla(NDM-1) plasmids (pPrY2001 and pKp11-42) was obtained using a 454-Genome Sequencer FLX. Contig assembly and gap closures were confirmed by PCR-based sequencing. Comparative analysis was done using BLASTn and BLASTp algorithms. RESULTS: Both clinical isolates were resistant to all ß-lactams, carbapenems, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole, and susceptible to tigecycline. Plasmid pPrY2001 (113 295 bp) was isolated from PR. It did not show significant homology to any known plasmid backbone and contained a truncated repA and novel repB. Two bla(NDM-1)-harbouring plasmids from Acinetobacter lwoffii (JQ001791 and JQ060896) shared 100% similarity to a 15 kb region that contained bla(NDM-1). pPrY2001 also contained a type II toxin/antitoxin system. pKp11-42 (146 695 bp) was isolated from KP. It contained multiple repA genes. The plasmid backbone had the highest homology to the IncFIIk plasmid type (51% coverage, 100% nucleotide identity). The bla(NDM-1) region was unique in that it was flanked upstream by IS3000 and downstream by a novel transposon designated Tn6229. pKp11-42 also contained a number of mutagenesis and plasmid stability proteins. CONCLUSIONS: pPrY2001 differed from all known plasmids due to its novel backbone and repB. pKp11-42 was similar to IncFIIk plasmids and contained a number of genes that aid in plasmid persistence.


Asunto(s)
ADN Bacteriano/genética , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/genética , Plásmidos , Providencia/enzimología , Providencia/genética , beta-Lactamasas/genética , Anciano , Canadá , ADN Bacteriano/química , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Providencia/aislamiento & purificación , Análisis de Secuencia de ADN
15.
Diabetologia ; 56(2): 350-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23192693

RESUMEN

AIMS/HYPOTHESIS: In this study, we used an immunodeficient mouse model to explore, in vivo, the longitudinal adaptation of human islets to an obesogenic environment. METHODS: Non-diabetic Rag2 (-/-) mice (n = 61) were transplanted with human islets (400 islet equivalents [IEQ]) from six pancreases: four non-diabetic and two with overt metabolic dysfunction (older, high HbA(lc) or history of diabetes). Animals were fed for 12 weeks with a control or high-fat diet (HFD), and followed for weight, serum triacylglycerol, fasting blood glucose and human C-peptide. After the mice were killed, human grafts and the endogenous pancreas were analysed for endocrine volume, distribution of beta and alpha cells, and proliferation. RESULTS: Transplanted mice on an HFD gained significantly more weight (p < 0.001) and had higher fasting glycaemia (2-12 weeks; p = 0.0002) and consistently higher fasting human C-peptide levels (2-12 weeks; p = 0.04) compared with those on the control diet. Histology demonstrated doubling of human islet graft volume at 12 weeks in animals on the HFD and increased beta cell volume (p < 0.001), but no change in alpha cell volume. Human islet function (hyperbolic product HOMA2%BS) at 12 weeks was four times lower in HFD animals (p < 0.001 vs controls) because of insufficient beta cell adaptation to decreased (70%) sensitivity (HOMA%S). Human islets obtained from donors with metabolic dysfunction failed to adapt to the HFD. CONCLUSIONS/INTERPRETATION: This longitudinal study provides direct evidence that human islets adapt both endocrine and beta cell mass, function and gene expression to obesity in vivo. The present model will facilitate the identification of mechanisms by which human islets adapt to obesity in vivo and the cell type(s) responsible, and factors predisposing human beta cells to decompensation.


Asunto(s)
Islotes Pancreáticos/fisiología , Animales , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Dieta Alta en Grasa/efectos adversos , Humanos , Inmunohistoquímica , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Trasplante de Islotes Pancreáticos , Masculino , Ratones , Obesidad/metabolismo , Reacción en Cadena de la Polimerasa
16.
Orthop Traumatol Surg Res ; 98(4): 432-40, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22578871

RESUMEN

INTRODUCTION: Double gloving is recommended in orthopedic surgery, notably in total hip arthroplasties (THA) to prevent contamination of the surgical site. HYPOTHESIS: Systematic glove changes during the key phases of hip prosthesis implantation reduce the frequency of occult perforations and bacterial loading of glove surfaces. PATIENTS AND METHODS: During 29 THA implantation procedures, we evaluated the bacterial contamination of the outer glove surface and its perforation rate. Contaminations were sought by placing the gloved fingertips on blood geloses (incubation, 48 h at 37°C), and perforations were sought using a water test (NF EN 455-1). RESULTS: One intervention was excluded from the study because an initial contamination was detected, leaving 28 cases analyzed. Fifteen interventions (53.6%) presented contaminated geloses (26 contaminated glove changes for 3.38% of the gloves used). These contaminations were found on the gloves of all of the gloved personnel, with no distinction as to the right or left side. Thirty-eight percent of the contaminations occurred during joint reduction, whereas the other surgical stages grouped 15-26% of the contaminations (P<0.05). Twenty-nine bacteria were identified: 62% coagulase-negative staphylococci (16% of which were methicillin-resistant). Twenty-eight perforations were identified (3.5% of the gloves used), 67.8% of which were located on the operator and 64.3% on the dominant side. Eighty percent of the perforations occurred during the "surgical incision" and the "cup and stem implantation" stages (respectively, 5.0% and 5.5% of the gloves used during the surgical time) (P<0.05), without being associated with an increased risk of bacterial contamination. At the 12-month clinical follow-up, no infectious complications were found. On the gloves worn by the 20 surgical team members contaminated during these 28 surgical procedures, replacing contaminated gloves with new sterile gloves rendered all the bacteriological samples of the subsequent surgical stages negative in 16 cases (80%). DISCUSSION: Increasing the number of outer glove renewals, notably during certain surgical stages at risk for contamination (prosthesis reduction) or perforation (surgical incision/femoral cementing) can reduce the risk of contamination and perforation. The bacteria isolated suggest a cutaneous origin. Regularly changing gloves has resulted in a sterile state in 80% of cases. LEVEL OF EVIDENCE AND TYPE OF STUDY: Level III prospective diagnostic study.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Bacterias/aislamiento & purificación , Guantes Quirúrgicos/microbiología , Infección de la Herida Quirúrgica/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Profilaxis Antibiótica , Antisepsia/métodos , Contaminación de Equipos , Falla de Equipo , Femenino , Prótesis de Cadera/microbiología , Humanos , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Paños Quirúrgicos , Infección de la Herida Quirúrgica/microbiología
17.
J Bone Joint Surg Br ; 94(4): 497-503, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22434466

RESUMEN

This prospective study compares the outcome of 157 hydroxyapatite (HA)-coated tibial components with 164 cemented components in the ROCC Rotating Platform total knee replacement in 291 patients. The mean follow-up was 7.6 years (5.2 to 11). There were two revisions for loosening: one for an HA-coated and one for a cemented tibial component. Radiological evaluation demonstrated no radiolucent lines with the HA-coated femoral components. A total of three HA-coated tibial components exhibited radiolucent lines at three months post-operatively and these disappeared after three further months of protected weight-bearing. With HA-coated components the operating time was shorter (p < 0.006) and the radiological assessment of the tibial interface was more stable (p < 0.01). Using revision for aseptic loosening of the tibial component as the end point, the survival rates at nine years was identical for both groups at 99.1%. Our results suggest that HA-coated components perform at least as well as the same design with cemented components and compare favourably with those of series describing cemented or porous-coated knee replacements, suggesting that fixation of both components with hydroxyapatite is a reliable option in primary total knee replacement.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Cementación/métodos , Materiales Biocompatibles Revestidos , Durapatita , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/instrumentación , Cementos para Huesos , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Prótesis de la Rodilla , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Falla de Prótesis , Radiografía , Reoperación , Resultado del Tratamiento
18.
Chir Main ; 31(2): 91-6, 2012 Apr.
Artículo en Francés | MEDLINE | ID: mdl-22381264

RESUMEN

OBJECTIVES: The aim of this study is the retrospective clinical evaluation of the arthroscopic treatments for triangular fibrocartilage complex tears. METHODS: Between 2003 and 2010, 76 patients with a traumatic lesion (Palmer type 1) and 25 patients with a degenerative lesion (Palmer type 2) of the triangular fibrocartilage complex underwent wrist arthroscopy. Clinical evaluations were based on the Mayo Modified Wrist Score (MMWS), on a compared measurement of the grip force and on a measurement of the different ranges of motion. We also made a subjective evaluation of the benefit brought by arthroscopy and a retrospective evaluation of the pre and postoperative pain. RESULTS: Mean MMWS was 86.3 for traumatic lesions and 83 for degenerative lesions. Mean grip force was 84.8 (Palmer type 1) and 84.2 (Palmer type 2) compared to the controlateral side. Mean ranges of flexion-extension, prosupination and radioulnar motions were 135°, 164° and 56° respectively for traumatic lesions and 130°, 156° and 54° respectively for degenerative lesions. Ninety-four percent of the operated patients reported an improvement of the symptomatology with better results for type 1 (98.7%) compared to type 2 (80%). We noted a clear diminution of the postoperative pain compared to the preoperative's one with frequently some mild persistent pain however. CONCLUSIONS: Arthroscopic treatments of the triangular fibrocartilage complex seem to be effective with an improvement of the symptomatology.


Asunto(s)
Artroscopía , Fibrocartílago Triangular/cirugía , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
19.
Epidemiol Infect ; 140(1): 172-81, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21396146

RESUMEN

Sporadic community-acquired legionellosis (SCAL) can be acquired through contaminated aerosols from residential potable water. Electricity-dependent hot-water tanks are widely used in the province of Quebec (Canada) and have been shown to be frequently contaminated with Legionella spp. We prospectively investigated the homes of culture-proven SCAL patients from Quebec in order to establish the proportion of patients whose domestic potable hot-water system was contaminated with the same Legionella isolate that caused their pneumonia. Water samples were collected in each patient's home. Environmental and clinical isolates were compared using pulsed-field gel electrophoresis. Thirty-six patients were enrolled into the study. Legionella was recovered in 12/36 (33%) homes. The residential and clinical isolates were found to be microbiologically related in 5/36 (14%) patients. Contaminated electricity-heated domestic hot-water systems contribute to the acquisition of SCAL. The proportion is similar to previous reports, but may be underestimated.


Asunto(s)
Infecciones Comunitarias Adquiridas/microbiología , Agua Potable/microbiología , Legionella pneumophila/aislamiento & purificación , Enfermedad de los Legionarios/microbiología , Abastecimiento de Agua/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Infecciones Comunitarias Adquiridas/epidemiología , Brotes de Enfermedades , Electroforesis en Gel de Campo Pulsado , Femenino , Humanos , Legionella pneumophila/clasificación , Legionella pneumophila/genética , Enfermedad de los Legionarios/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Quebec/epidemiología , Estaciones del Año , Temperatura
20.
Orthop Traumatol Surg Res ; 97(2): 211-6, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21273155

RESUMEN

UNLABELLED: We report on seven traumatic lesions of the tibialis anterior tendon (one subcutaneous rupture and six open tears) in seven injured patients of mean age 45 years [17-79] all managed by direct suture and immobilization either using a cast boot (four cases) or a lower leg external fixator (three cases). After a mean follow-up of 31 months (6-50), external fixation achieved favourable clinical results with no specific complication. External fixation improves the conditions for suture efficiency, provides full immobilization and facilitates wound care in patients at a high risk of developing cutaneous complications. In accordance with data published in the literature, immobilization by means of a windowed cast boot achieved satisfactory results in patients with no risk factors. This method compatible with early mobilization avoids placement of a posterior splint which could induce slackening and weakening of tendon repair. LEVEL OF EVIDENCE: Retrospective study (Level IV).


Asunto(s)
Inmovilización/métodos , Traumatismos de los Tendones/cirugía , Adolescente , Adulto , Anciano , Moldes Quirúrgicos , Fijadores Externos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rotura , Técnicas de Sutura
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